Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target?

Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and – despite many unanswered questions – therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial. We clearly need to understand better the mechanisms that underlie MODS. The endothelium certainly plays an active role in MODS. It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration. An important regulator of these systems is the angiopoietin/Tie2 signalling system. In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy

Towards a feasible algorithm for tight glycaemic control in critically ill patients: a systematic review of the literature

INTRODUCTION: Tight glycaemic control is an important issue in the management of intensive care unit (ICU) patients. The glycaemic goals described by Van Den Berghe and colleagues in their landmark study of intensive insulin therapy appear difficult to achieve in a real life ICU setting. Most clinicians and nurses are concerned about a potentially increased frequency of severe hypoglycaemic episodes with more stringent glycaemic control. One of the steps we took before we implemented a glucose regulation protocol was to review published trials employing insulin/glucose algorithms in critically ill patients. METHODS: We conducted a search of the PubMed, Embase and Cochrane databases using the following terms: 'glucose', 'insulin', 'protocol', 'algorithm', 'nomogram', 'scheme', 'critically ill' and 'intensive care'. Our search was limited to clinical trials conducted in humans. The aim of the papers selected was required to be glycaemic control in critically ill patients; the blood glucose target was required to be 10 mmol/l or under (or use of a protocol that resulted in a mean blood glucose = 10 mmol/l). The studies were categorized according to patient type, desired range of blood glucose values, method of insulin administration, frequency of blood glucose control, time taken to achieve the desired range for glucose, proportion of patients with glucose in the desired range, mean blood glucose and frequency of hypoglycaemic episodes. RESULTS: A total of twenty-four reports satisfied our inclusion criteria. Most recent studies (nine) were conducted in an ICU; nine others were conducted in a perioperative setting and six were conducted in patients with acute myocardial infarction or stroke. Studies conducted before 2001 did not include normoglycaemia among their aims, which changed after publication of the study by Van Den Berghe and coworkers in 2001; glycaemic goals became tighter, with a target range between 4 and 8 mmol/l in most studies. CONCLUSION: Studies using a dynamic scale protocol combining a tight glucose target and the last two blood glucose values to determine the insulin infusion rate yielded the best results in terms of glycaemic control and reported low frequencies of hypoglycaemic episodes

Quality of interhospital transport of critically ill patients: a prospective audit

INTRODUCTION: The aim of transferring a critically ill patient to the intensive care unit (ICU) of a tertiary referral centre is to improve prognosis. The transport itself must be as safe as possible and should not pose additional risks. We performed a prospective audit of the quality of interhospital transports to our university hospital-based medical ICU. METHODS: Transfers were undertaken using standard ambulances. On departure and immediately after arrival, the following data were collected: blood pressure, heart rate, body temperature, oxygen saturation, arterial blood gas analysis, serum lactic acid, plasma haemoglobin concentration, blood glucose, mechanical ventilation settings, use of vasopressor/inotropic drugs, and presence of venous and arterial catheters. Ambulance personnel completed forms describing haemodynamic and ventilatory data during transport. Data were collected by our research nurse and analyzed. RESULTS: A total of 100 consecutive transfers of ICU patients over a 14-month period were evaluated. Sixty-five per cent of patients were mechanically ventilated; 38% were on vasoactive drugs. Thirty-seven per cent exhibited an increased number of vital variables beyond predefined thresholds after transport compared with before transport; 34% had an equal number; and 29% had a lower number of vital variables beyond thresholds after transport. The distance of transport did not correlate with the condition on arrival. Six patients died within 24 hours after arrival; vital variables in these patients were not significantly different from those in patients who survived the first 24 hours. ICU mortality was 27%. Adverse events occurred in 34% of transfers; in 50% of these transports, pretransport recommendations given by the intensivist of our ICU were ignored. Approximately 30% of events may be attributed to technical problems. CONCLUSION: On aggregate, the quality of transport in our catchment area carried out using standard ambulances appeared to be satisfactory. However, examination of the data in greater detail revealed a number of preventable events. Further improvement must be achieved by better communication between referring and receiving hospitals, and by strict adherence to checklists and to published protocols. Patients transported between ICUs are still critically ill and should be treated as such

Accuracy and feasibility of point-of-care and continuous blood glucose analysis in critically ill ICU patients

INTRODUCTION: To obtain strict glucose regulation, an accurate and feasible bedside glucometry method is essential. We evaluated three different types of point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The study was performed as a single-centre, prospective, observational study in a 12-bed medical ICU of a university hospital. METHODS: Patients with an expected ICU stay of more than 48 hours were included. Because the reference laboratory delivers glucose values after approximately 30 to 60 minutes, which is too slow to use in a glucose regulation protocol and for calibration of the subcutaneous continuous glucose monitoring system (CGMS) (CGMS System Gold), we first validated the ICU-based blood gas/glucose analyser ABL715 (part 1 of the study). Subsequently, part 2 was performed: after inserting (and calibrating) the subcutaneous CGMS, heparinised arterial blood samples were drawn from an arterial line every 6 hours and analysed on both the Precision PCx point-of-care meter using test strips and on the blood gas/glucose analyser ABL715. CGMS glucose data were downloaded after 24 to 72 hours. The results of the paired measurements were analysed as a scatter plot by the method of Bland and Altman and were expressed as a correlation coefficient. RESULTS: Part 1: Four hundred and twenty-four blood samples were drawn from 45 critically ill ICU patients. The ICU-based blood gas/glucose analyser ABL715 provided a good estimate of conventional laboratory glucose assessment: the correlation coefficient was 0.95. In the Clarke error grid, 96.8% of the paired measurements were in the clinically acceptable zones A and B. Part 2: One hundred sixty-five paired samples were drawn from 19 ICU patients. The Precision PCx point-of-care meter showed a correlation coefficient of 0.89. Ninety-eight point seven percent of measurements were within zones A and B. The correlation coefficient for the subcutaneous CGMS System Gold was 0.89. One hundred percent of measurements were within zones A and B. CONCLUSION: The ICU-based blood glucose analyser ABL715 is a rapid and accurate alternative for laboratory glucose determination and can serve as a standard for ICU blood glucose measurements. The Precision PCx is a good alternative, but feasibility may be limited because of the blood sample handling. The subcutaneous CGMS System Gold is promising, but real-time glucose level reporting is necessary before it can be of clinical use in the ICU. When implementing a glucose-insulin algorithm in patient care or research, one should realise that the absolute glucose level may differ systematically among various measuring methods, influencing targeted glucose levels